Poly-α-hydroxy acids are biodegradable polymers and they are hydrolyzed in vivo. In natural environments, they are metabolized/decomposed into water and a carbon dioxide gas with an aid of microorganisms. In recent days, poly-α-hydroxy acids have therefore drawn attentions as eco-friendly polymer materials. Of these, polylactic acid and polyglycolic acid have drawn attentions as eco-friendly polymer materials to be used instead of medical materials or general-purpose resins. In particular, polyglycolic acid has attracted attentions as a polymer material to be used for gas barrier applications due to its typical properties, that is, gas barrier properties.
Since it is difficult to obtain a high-molecular-weight poly-α-hydroxy acid directly by dehydration condensation of an α-hydroxy acid, a process for obtaining a high-molecular-weight poly-α-hydroxy acid by preparing a cyclic dimer ester first and then carrying out ring-opening polymerization is known. In the case of the production of, for example, polylactic acid or polyglycolic acid, it is known to produce it by synthesizing lactide or glycolide which is a cyclic dimer ester and then subjecting the lactide or glycolide to ring-opening polymerization in the presence of a catalyst. It is however necessary to use high-purity lactide or glycolide in order to obtain high-molecular-weight polylactic acid or polyglycolic acid by ring-opening polymerization of lactide or glycolide. As a process for obtaining high-purity lactide or glycolide from lactic acid or glycolic acid, there is disclosed a process for synthesizing a lactic acid or glycolic acid oligomer and then depolymerizing it in a polar organic solvent having a high boiling point (Patent Document 1).
In the process for depolymerizing a glycolic acid oligomer to prepare glycolide, a trace amount of alkali metal ions contained in the oligomer becomes a cause for destabilizing the depolymerization reaction system, but long-term stability of the depolymerization reaction can be achieved by adding, to the reaction system, a sulfate salt or organic acid salt of divalent or higher-valent cations even in the presence of the alkali metal ions (Patent Document 2).
Thus, α-hydroxy acids which will serve as raw materials of the corresponding poly-α-hydroxy acids are obtainable by converting α-hydroxy acid ammonium salts into the corresponding α-hydroxy acids.
As the most common process for converting carboxylic acid ammonium salts into the corresponding carboxylic acids, a process of adding a strong acid such as sulfuric acid to the salts, thereby obtaining both free acids and by-product ammonium sulfate can be given. A process of producing a large amount of waste products such as ammonium sulfate is however undesirable from an environmental standpoint.
As a process for converting carboxylic acid ammonium salts into the corresponding carboxylic acids, there are disclosed a process of producing an α-hydroxycarboxylic acid by thermally hydrolyzing its ammonium salt, and taking, out of the system, both an inert gas and an ammonia gas which is a product, thereby shifting equilibrium to the side of the reaction product obtained by thermal hydrolysis (Patent Document 3) and a process of producing 2-hydroxy-4-methylthiobutanoic acid from ammonium 2-hydroxy-4-methylthiobutanoate by heating it under pressure, thereby accelerating a shift of equilibrium to the side of the reaction product of thermal hydrolysis and evaporating ammonia with water (Patent Document 4).
Thermal hydrolysis of an ammonium carboxylate needs, however, a great deal of energy and in addition, it takes much time to carry out 100% conversion into its free acid so that thermal hydrolysis is not a practical process. When ammonia is removed from an ammonium carboxylate only by thermal hydrolysis, energy enough for separating the bond between carboxylate anions and ammonium cations is required. As the amount of ammonium cations gets smaller, the energy necessary for separation increases, which makes the separation more difficult. Moreover, heat treatment of an ammonium carboxylate produces the corresponding carboxylic acid amide, which leads to a serious problem in consideration of the quality of the final product.
Not a simple thermal hydrolysis but a process using some sort of a reactant is therefore proposed. For example, there is disclosed a process of reacting ammonium succinate with an alcohol or water to eliminate ammonia and obtaining succinic acid or a derivative thereof while collecting the ammonia thus eliminated (Patent Document 5). The reaction with an alcohol however produces a succinate ester, which requires hydrolysis again and therefore complicates the preparation step.
There is also disclosed a process of heating and decomposing ammonium lactate in the presence of an organic amine which is immiscible in water and preparing a reaction product containing lactic acid and the organic amine (Patent Document 6). Although this process can certainly remove ammonia from the ammonium salt, further purification is necessary for obtaining a high-purity free acid from the resulting mixture with the organic amine. Accordingly, it can be expected easily that it may complicate the preparation step.
There is also disclosed a process of producing α-hydroxy-4-methylthiobutyric acid by heating ammonium α-hydroxy-4-methylthiobutyrate, which has been obtained by biologically hydrolyzing α-hydroxy-4-methylthiobutyronitrile and then concentrating the hydrolysate, in an ether solvent having two or more ether bonds and distilling off the thus-liberated ammonia (Patent Document 7). Although this process enables removal of ammonia from the ammonium salt to reduce the residual ratio of ammonia to about 0.12%, this process produces a carboxylic acid, which leads to a serious problem in consideration of the quality of the final product.
There is also proposed a process of removing ammonia by utilizing a dehydration condensation reaction of a hydroxycarboxylic acid itself without adding an extraneous reactant. For example, there is disclosed a process comprising a first step of heating ammonium α-hydroxy-4-methylthiobutyrate to convert it into a low-molecular-weight poly-α-hydroxy-4-methylthiobutyric acid while removing water and ammonia and a second step of adding water to it and heating the resulting mixture to hydrolyze the low-molecular-weight polymer into the corresponding free acid (Patent Document 8). Production of the amide as a by-product in the first step is, however, inevitable and a portion of it becomes ammonium α-hydroxy-4-methylthiobutyrate as a result of the hydrolysis in the second step. Ammonia cannot therefore be removed enough to raise the purity. In addition, the conversion ratio by the hydrolysis reaction in the second step does not reach 100% and a portion of the low-molecular-weight poly-α-hydroxy-4-methylthiobutyric acid remains and poses a quality problem. In fact, Patent Document 8 describes therein that the purity is approximately 80% and purification such as extraction is necessary to obtain an α-hydroxy acid with a higher purity.
A process using an ion exchange resin is also proposed. There is disclosed, for example, a process of obtaining a carboxylic acid by adsorbing ammonium cations of an aqueous solution of ammonium methacrylate to a cation exchange resin and collecting the ammonium cations thus adsorbed to the resin as ammonia by using an organic solvent (Patent Document 9). The ammonia decomposition ratio does not reach a satisfactory level and therefore this process is far from an industrially usable process.
As a further process, there is also disclosed a process of collecting a carboxylic acid and ammonia from the corresponding ammonium carboxylate by electrodialysis using a system composed of a bipolar membrane, an anion membrane, and a bipolar membrane (Patent Document 10). If a carboxylic acid amide is contained as an impurity, however, it prevents purification using electrodialysis or even if it does not prevent the purification, the carboxylic acid amide accumulates in a recycled liquid.
Moreover, there is proposed a process of obtaining, from an ammonium salt of a carboxylic acid such as dicarboxylic acid, tricarboxylic acid or amino acid, the free acid by reaction crystallization using a volatile carboxylic acid having a lower ionization exponent than that of the above-described carboxylic acid and collecting the volatile acid from an ammonium salt of the volatile acid contained in the mother liquor (Patent Document 11). It is however difficult to completely remove the ammonia in the crystals of the free acid thus obtained. An inevitable residue of from about 2 to 3% of the ammonia poses a quality problem.
An α-hydroxy acid ammonium salt can be synthesized, for example, from an α-hydroxynitrile compound. Synthesis of a carboxylic acid compound from the α-hydroxynitrile compound can be performed using a biocatalyst having nitrile hydrolysis activity. Examples of the biocatalyst having nitrile hydrolysis activity and capable of converting a nitrile compound into a carboxylic acid compound include nitrilase and combination of nitrile hydratase and amidase.
The above-described process is advantageous because a reaction process can be simplified due to mild reaction conditions and a high-purity reaction product containing a relatively small amount of by-products can be prepared. Use of it for the preparation of various carboxylic acid compounds has therefore been investigated in recent years. Although the amount of by-products is not so much, impurities, for example, nitriles such as α-aminonitrile and iminodialkylnitrile, and amides or carboxylic acids which are hydrolysates thereof are produced by the hydrolysis of α-hydroxynitrile compounds.
The product obtained by the reaction is an ammonium carboxylate irrespective of the kind of the biocatalyst so that the ammonium carboxylate must be converted into the corresponding carboxylic acid by the above-described method. Also in this step, impurities such as α-hydroxy acid amide remain.
As an example utilizing a nitrile compound, there is proposed a process of producing a calcium α-hydroxycarboxylate from an ammonium α-hydroxycarboxylate which has been prepared from an α-hydroxynitrile by using a biocatalyst. Described specifically, there is disclosed a process of producing calcium 2-hydroxy-4-methylthiobutanoate by bringing a calcium source into contact with ammonium 2-hydroxy-4-methylthiobutanoate obtainable by the biological hydrolysis of 2-hydroxy-4-methylthiobutylonitrile (Patent Document 12). This Document however supposes the use of calcium 2-hydroxy-4-methylthiobutanoate as is as a feed additive and does not disclose the production of 2-hydroxy-4-methylthiobutanoic acid by desalting the calcium 2-hydroxy-4-methylthiobutanoate or production of a poly-α-hydroxy acid using 2-hydroxy-4-methylthiobutanoic acid as a raw material. Accordingly, as a matter of fact, it mentions neither the influence of impurities in an α-hydroxy acid on the preparation of the corresponding poly-α-hydroxy acid nor conditions for obtaining an α-hydroxy acid most suited as a polymer raw material.
There is also disclosed a process of reacting an α-hydroxynitrile with a microorganism having a nitrile hydrating capacity or a processed product thereof to yield the corresponding α-hydroxy acid amide and/or α-hydroxy acid ammonium salt, hydrolyzing the α-hydroxy acid amide in the presence of a base while subjecting the α-hydroxy acid ammonium salt to salt exchange, thereby producing the corresponding salt of the α-hydroxy acid, and carrying out, after removal of ammonia, electrodialysis to prepare the α-hydroxy acid and base (Patent Document 13). This document describes, in Examples, only a production example of 2-hydroxy-4-methylthiobutanoic acid to be used as is for animal feed or the like. It never describes the production of a poly-α-hydroxy acid from calcium 2-hydroxy-4-methylthiobutanoate. There is therefore no description on the conditions for obtaining the most suited α-hydroxy acid as a polymer raw material.
Even if the process disclosed in Patent Document 12 or 13 is employed, it is just conceivable that impurities, for example, nitriles such as α-aminonitrile and iminodialkylnitrile which are presumed to be by-products of the hydrolysis of an α-hydroxy acid amide or α-hydroxynitrile, or amides or carboxylic acids which are hydrolysates of the nitriles may remain in a final product of an α-hydroxy acid. These impurities have a serious influence on the quality of the α-hydroxy acid to be used as a polymer raw material but these documents do not describe the conditions permitting sufficient removal of these impurities.    [Patent Document 1] Japanese Patent Laid-Open No. Hei 9-328481    [Patent Document 2] Japanese Patent Laid-Open No. 2004-519485    [Patent Document 3] WO200059847 A1    [Patent Document 4] Japanese Patent Laid-Open No. 2000-119214    [Patent Document 5] Japanese Patent Laid-Open No. 2005-132836    [Patent Document 6] Japanese Patent Laid-Open No. 2004-532855    [Patent Document 7] WO199900350 A1    [Patent Document 8] WO199730962 A1    [Patent Document 9] Japanese Patent Laid-Open No. Sho 62-23823    [Patent Document 10] U.S. Pat. No. 581,449 A1    [Patent Document 11] Japanese Patent Laid-Open No. 2004-196768    [Patent Document 12] Japanese Patent Laid-Open No. Hei 11-75885    [Patent Document 13] Japanese Patent Laid-Open No. 10-179183